The American Society for Microbiology (ASM) submits the following comments on the November 27, 2012 Proposed Framework for Guiding HHS Funding Decisions about Highly Pathogenic Avian Influenza H5N1 Gain-of-Function Research. The ASM is the largest single life science Society with over 36,000 members. ASM has followed and participated in the ongoing discussions of HPAI H5N1 research, and has sponsored national and international meetings on this topic. In addition, ASM journals have published articles that discuss biosecurity and biosafety related to HPAI H5N1 gain-of-function research. The Framework is an issue of great importance to ASM members, since they will be directly and indirectly impacted by the proposed concepts it embodies.

A number of public health benefits can be obtained by gain-of-function research, including the development and assessment of vaccines, therapeutics, diagnostics, and surveillance methodologies that protect the public against naturally occurring and unnaturally occurring pandemics. The ASM firmly believes there is value in conducting gain-of-function research with HPAI H5N1 as long as the benefits outweigh the risks. We also agree that it has been prudent for the research community to execute a worldwide moratorium, allowing dialogue about how best to proceed with the safe conduct of gain-of-function HPAI H5N1 research.

The proposed Framework for HHS funding decisions regarding such research is an important step that should provide a path forward to continue H5N1 research safely. However, it is essential that the Framework be crafted carefully, to assure the public and the scientific community that responsible decision-making will allow the safe conduct of research needed to advance our preparedness against lethal strains of influenza. The content and scope of the Framework is critically important because it will serve as the prototype for future protocols regarding gain-of-function research using agents listed in Section III of the USG Policy for Oversight of Life Sciences Dual Use Research of Concern.

The ASM fully understands the importance of a well-informed culture of responsibility surrounding any efforts in gain-of-function research. We also support efforts directed toward international harmonization of guidelines, open exchange of scientific information, and avoidance of multiple framework documents. However, the proposed Framework presents several concerns with regard to process and criteria to meet this complex challenge. The following are ASM’s specific concerns with the proposed Framework for HPAI H5N1 research:

The process for departmental review is inadequately defined. This makes it difficult for ASM to understand how it will be operationalized. It does not specify who will lead the review, who will actually perform the review, or the timeframe in which it should be conducted. A time certain for the review should be given to assure the committee does not serve as an impediment to initiating the research. The Framework should clearly define who would be involved in an HHS departmental review and whether (and which) additional departments and agencies would be involved. The role of these other agencies should be specified and the Framework should state how the review would ensure that there is adequate internal and external expertise. Although described as an HHS departmental level review, subsequent information suggests it will involve multiple agencies; it should therefore be referred to as an interagency review. We maintain that it is absolutely essential that appropriate scientific expertise, both internal and external, be part of the review process. It is not clear why the funding agency review would be followed by a departmental level review, nor why this second, higher level of review would not be conducted by, or at least informed by, the NSABB―the board specifically created to provide HHS and other federal departments with advice from board members with scientific, public health and biosecurity expertise. The NSABB has the technical expertise needed to provide credible advice that would balance the scientific and public health merits of the research with any biosafety or biosecurity concerns (including DURC). The ASM has concerns about the absence of a mention or a role of the NSABB in the proposed framework. If the NSABB is not functioning as originally designed, any functional deficiencies should be examined and corrected.

The normal outcome of agency review (e.g., by the NIH) is to either fund or not to fund a proposal. If a proposal is not funded, the reasons are given to the investigator. This should be the standard process for gain-of-function HPAI H5N1 research proposals as well. ASM has significant concerns about the HHS, or interagency review, rendering decisions about whether the research should be conducted in a classified manner or referring the research proposal to another governmental agency which is able to support or conduct classified research. Many universities will not perform classified research and the interagency committee should not be suggesting they do so. If the research is truly for advancing public health, then HHS/NIH should either fund it, if the benefits outweigh the risks, or HHS should not fund it and should inform the investigator(s) and the institution(s) of the reasons for not funding, which might be that the risks (e.g., biosafety or DURC) are considered to be greater than the benefits. It should then be up to the investigator(s) and the institution(s) to decide whether to modify the proposal and resubmit to an HHS agency, to submit to another department that might fund the research in a classified manner, or to not further advance the research idea. As stated in National Security Directive 189, it is in the public interest that fundamental research results should remain unrestricted. If restrictions are imposed on the publication of HPAI H5N1research and dissemination of new knowledge is constrained, the research will lose its exemption under the Export Administration Regulations and will then be subject to export control.

The criteria (Box 2) in the proposed Framework for determining whether a research proposal requires higher level review are ambiguous, especially Criterion 2. Criterion 2 states that gain-of-function research should not be done “unless there is evidence that such a virus could be produced through a natural evolutionary process in the foreseeable future.” This is highly speculative, as it is difficult (if not impossible) for an investigator to make such a claim. ASM suggests that this criterion should be dropped or substantially modified to remove ambiguity.

Thank you for the opportunity to comment. The ASM stands ready to assist the NIH and the HHS in any way possible.